Purification, characterization, and localization of a novel trypsin-like protease found in the human airway.

Yasuoka, Susumu; Ohnishi, Tsukasa; Kawano, Sachiko; Tsuchihashi, Sumiko; Ogawara, Mitsumasa; Masuda, Kenichi; Yamaoka, Kaoru; Takahashi, Masako; Sendo, Toshiaki

doi:10.1165/ajrcmb.16.3.9070615

Cited by 111 publications

(141 citation statements)

References 34 publications

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“…This had been isolated from the sputum of patients with chronic airway disease and was named human airway trypsin-like protease (HAT). It had an identical catalytic subunit to AsP but instead of having a secretory signal sequence, contained a type II transmembrane domain at the N-terminal (Yasuoka et al 1997). The question of whether HAT represented the human homolog of AsP was addressed by Hansen et al (2004).…”

Section: Identification Of An Enzyme That Cleaves Pro-γ-msh During Comentioning

confidence: 99%

60 YEARS OF POMC: N-terminal POMC peptides and adrenal growth

Bicknell

2016

Journal of Molecular Endocrinology

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The peptide hormones contained within the sequence of proopiomelanocortin (POMC) have diverse roles ranging from pigmentation to regulation of adrenal function to control of our appetite. It is generally acknowledged to be the archetypal hormone precursor, and as its biology has been unravelled, so too have many of the basic principles of hormone biosynthesis and processing. This short review focuses on one group of its peptide products, namely, those derived from the N-terminal of POMC and their role in the regulation of adrenal growth. From a historical and a personal perspective, it describes how their role in regulating proliferation of the adrenal cortex was identified and also highlights the key questions that remain to be answered.

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Section: Identification Of An Enzyme That Cleaves Pro-γ-msh During Comentioning

confidence: 99%

60 YEARS OF POMC: N-terminal POMC peptides and adrenal growth

Bicknell

2016

Journal of Molecular Endocrinology

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“…22 Activated TTSPs are predicted to remain membranebound through a conserved disulphide bond linking the pro-and catalytic domains. Interestingly, soluble forms of enteropeptidase, 23 HAT, 24 TMPRSS2, 21 and matriptase 19 have been isolated in vivo. Shedding from the cell surface for porcine enteropeptidase and murine matriptase is mediated through proteolytic processing at the respective cleavage sites, 117 GSVIV and 149 GSVIA, within the SEA (Sea urchin sperm protein, Enteropeptidase, Agrin) domains of their stem regions.…”

Section: The Type II Transmembrane Serine Proteasesmentioning

confidence: 99%

“…14 The largest of the sub-families, HAT/DESC (Differentially Expressed in Squamous cell Carcinoma) consists of the proteases HAT, DESC1-4 10,41,42 and HATlike 3-5. 43 HAT was originally purified from the sputum of patients with chronic airway diseases 24 and is proposed to be associated with mucus production 44 and fibrin deposition within airways. 45 Further, elevated levels of HAT are present in the epidermis of psoriasis patients, suggesting an inflammatory role for this enzyme.…”

Section: The Type II Transmembrane Serine Proteasesmentioning

confidence: 99%

Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis

Ramsay¹,

Hooper²,

Folgueras³

et al. 2009

Haematologica

107

104

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Maintaining the body's levels of iron within precise boundaries is essential for normal physiological function. Alterations of these levels below or above the healthy limit lead to a systemic deficiency or overload in iron. The type-two transmembrane serine protease (TTSP), matriptase-2 (also known as TMPRSS6), is attracting significant amounts of interest due to its recently described role in iron homeostasis. The finding of this regulatory role for matriptase-2 was originally derived from the observation that mice deficient in this protease present with anemia due to elevated levels of hepcidin and impaired intestinal iron absorption. Further in vitro analysis has demonstrated that matriptase-2 functions to suppress bone morphogenetic protein stimulation of hepcidin transcription through cell surface proteolytic processing of the bone morphogenetic protein co-receptor hemojuvelin. Consistently, the anemic phenotype of matriptase-2 knockout mice is mirrored in humans with matripase-2 mutations. Currently, 14 patients with iron-refractory iron deficiency anemia (IRIDA) have been reported to harbor various genetic mutations that abrogate matriptase-2 proteolytic activity. In this review, after overviewing the membrane anchored serine proteases, in particular the TTSP family, we summarize the identification and characterization of matriptase-2 and describe its functional relevance in iron metabolism.

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“…Trypsin is the most potent PAR2 agonist, and trypsin-like enzymes have been detected in airway epithelial cells (8,11) and in airway secretions (11,45). The purification and characterization of these enzymes is required to ascertain their effectiveness as PAR2 agonists.…”

Section: Tryptase and Trypsin May Activate Par2 In The Inflamed Airwaymentioning

confidence: 99%

Protease-Activated Receptor 2 Mediates Eosinophil Infiltration and Hyperreactivity in Allergic Inflammation of the Airway

Schmidlin

Amadesi

Dabbagh³

et al. 2002

The Journal of Immunology

305

260

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Trypsin and mast cell tryptase can signal to epithelial cells, myocytes, and nerve fibers of the respiratory tract by cleaving proteinase-activated receptor 2 (PAR2). Since tryptase inhibitors are under development to treat asthma, a precise understanding of the contribution of PAR2 to airway inflammation is required. We examined the role of PAR2 in allergic inflammation of the airway by comparing OVA-sensitized and -challenged mice lacking or overexpressing PAR2. In wild-type mice, immunoreactive PAR2 was detected in airway epithelial cells and myocytes, and intranasal administration of a PAR2 agonist stimulated macrophage infiltration into bronchoalveolar lavage fluid. OVA challenge of immunized wild-type mice stimulated infiltration of leukocytes into bronchoalveolar lavage and induced airway hyperreactivity to inhaled methacholine. Compared with wild-type animals, eosinophil infiltration was inhibited by 73% in mice lacking PAR2 and increased by 88% in mice overexpressing PAR2. Similarly, compared with wild-type animals, airway hyperreactivity to inhaled methacholine (40 μg/ml) was diminished 38% in mice lacking PAR2 and increased by 52% in mice overexpressing PAR2. PAR2 deletion also reduced IgE levels to OVA sensitization by 4-fold compared with those of wild-type animals. Thus, PAR2 contributes to the development of immunity and to allergic inflammation of the airway. Our results support the proposal that tryptase inhibitors and PAR2 antagonists may be useful therapies for inflammatory airway disease.

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Purification, characterization, and localization of a novel trypsin-like protease found in the human airway.

Cited by 111 publications

References 34 publications

60 YEARS OF POMC: N-terminal POMC peptides and adrenal growth

60 YEARS OF POMC: N-terminal POMC peptides and adrenal growth

Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis

Protease-Activated Receptor 2 Mediates Eosinophil Infiltration and Hyperreactivity in Allergic Inflammation of the Airway

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